Submissions for variant NM_201525.4(ADGRG1):c.286C>T (p.Arg96Ter)

gnomAD frequency: 0.00001  dbSNP: rs146278035

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000146051	SCV000193206	pathogenic	Bilateral frontoparietal polymicrogyria	2013-02-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000624486	SCV000741122	pathogenic	Inborn genetic diseases	2015-11-17	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000146051	SCV001429594	likely pathogenic	Bilateral frontoparietal polymicrogyria	2019-02-08	criteria provided, single submitter	clinical testing
Invitae	RCV001389682	SCV001591132	pathogenic	not provided	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg96*) in the ADGRG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRG1 are known to be pathogenic (PMID: 15044805, 20929962). This variant is present in population databases (rs146278035, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ADGRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 158629). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001389682	SCV003831675	likely pathogenic	not provided	2022-03-23	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000146051	SCV004171936	likely pathogenic	Bilateral frontoparietal polymicrogyria		criteria provided, single submitter	clinical testing	The stop gained c.286C>T(p.Arg96Ter) variant in ADGRG1 gene has been reported previously in ClinVar database as Likely pathogenic/Pathogenic (multiple submissions). The variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. The nucleotide change c.286C>T in ADGRG1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. Functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic.